Potassium Carbonate → 5-Chloro-N-[4-(cyano-dimethyl-methyl)-benzyl]-2-(4-fluoro-phenoxy)-nicotinamide

HRID 1297594Notes

Reaction equation

HRID 1297594 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][C:5]([O:22][C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)=[C:6]([CH:21]=1)[C:7]([NH:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([C:17](O)([CH3:19])[CH3:18])=[CH:13][CH:12]=1)=[O:8].C[Si]([C:34]#[N:35])(C)C.[Sn](Cl)(Cl)(Cl)Cl.C(=O)([O-])[O-].[K+].[K+].O.O.[F-].[K+]>ClCCl.O>[Cl:1][C:2]1[CH:3]=[N:4][C:5]([O:22][C:23]2[CH:24]=[CH:25][C:26]([F:29])=[CH:27][CH:28]=2)=[C:6]([CH:21]=1)[C:7]([NH:9][CH2:10][C:11]1[CH:12]=[CH:13][C:14]([C:17]([C:34]#[N:35])([CH3:19])[CH3:18])=[CH:15][CH:16]=1)=[O:8]

Participants

8

Reactant 5

HCID 11430Potassium CarbonateHCID 24287Tin tetrachlorideHCID 82115Trimethylsilyl cyanideHCID 23708904Potassium fluoride dihydrateHCID 589151875-Chloro-2-(4-fluoro-phenoxy)-N-[4-(1-hydroxy-1-methyl-ethyl)-benzyl]-nicotinamide

Product 1

HCID 178328335-Chloro-N-[4-(cyano-dimethyl-methyl)-benzyl]-2-(4-fluoro-phenoxy)-nicotinamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

5-Chloro-2-(4-fluoro-phenoxy)-N-[4-(1-hydroxy-1-methyl-ethyl)-benzyl]-nicotinamide (1.61 g) was dissolved in anhydrous dichloromethane (40 mL) and cooled to 0° C. in an ice bath. Trimethylsilyl cyanide (7.8 mL) was added, followed by tin(IV)chloride (1.0 M solution in dichloromethane; 1.6 mL) added slowly over 15 min. The reaction mixture was sealed under nitrogen and allowed to warm slowly to ambient temperature overnight while stirring. Potassium carbonate (7.56 g), potassium fluoride dihydrate (0.902 g), and water (1.95 mL) were then added. The resulting mixture was stirred for 90 min, then silica gel (3.22 g) was added and the slurry stirred for another 30 minutes. The solids were removed by filtration and the filtrate concentrated to dryness in vacuo to yield the crude title compound (0.850 g).

Workup

  1. additionadded slowly over 15 min
  2. customThe reaction mixture was sealed under nitrogen
  3. temperatureto warm slowly to ambient temperature overnight
  4. stirringThe resulting mixture was stirred for 90 min
  5. additionsilica gel (3.22 g) was added
  6. stirringthe slurry stirred for another 30 minutes
  7. customThe solids were removed by filtration
  8. concentrationthe filtrate concentrated to dryness in vacuo

Sources & evidence

ORD record
ord-36a7327ee6dc4dbc91d72784dd1979e8
Source dataset
uspto-grants-2007_07
Patent number
US07250518B2

Reaction notes

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